Multiple abnormalities due to a nonsense mutation in the Alx4 gene
Multiple abnormalities due to a nonsense mutation in the Alx4 gene
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Alx4 基因无义突变导致多种异常。
DOI：
10.4238/2013.august.2.2
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发表时间：
2013-01-01
影响因子：
0.4
通讯作者：
Xue, Z. F.
中科院分区：
文献类型：
--
作者：
Chen, B.;Chen, Lu;Xue, Z. F.
肢体前后轴的模式取决于来自肢体芽的三个信号中心的几个信号。这些信号相互作用，构成一个复杂而有序的网络，对肢芽的发育起着至关重要的作用。小鼠轴前型多指畸形主要是由于极化活动区或Sonic hedgehog在肢芽前部的异位表达引起的。在这项研究中，我们描述了一个N-乙基-N-亚硝基脲诱导的多趾小鼠（Alx 4 m1 Yzcm）的一个或两个后趾的前面额外的数字。该突变定位于2号染色体，位于标记D2 Mit 45和D2 Mit 184之间。Alx 4基因被确定为该位置的潜在候选基因。多指杂合子的Alx 4基因的序列分析揭示了A/T颠换突变，导致在位置145处用终止（无义）密码子取代赖氨酸密码子。Alx 4 m1 Yzcm纯合子小鼠表现出多种异常，包括四肢广泛的轴前多指（趾）（最多7指）和脐膨出的形成。
Patterning of the limb anterior-posterior axes depends on several signals that derive from the three signaling centers of the limb bud. These signals interact to constitute a complex and ordered network that critically contributes to the development of limb buds. Preaxial polydactyly in mouse is predominantly caused by ectopic expression of the zone of polarizing activity or Sonic hedgehog in the anterior region of the limb bud. In this study, we describe an N-ethyl-N-nitrosourea-induced polydactylous mouse (Alx4m1Yzcm) with an extra digit on the anterior aspect of one or two hinddigits. The mutation was mapped to chromosome 2, between markers D2Mit45 and D2Mit184. The Alx4 gene was identified as a potential candidate gene in this location. Sequence analysis of the Alx4 gene for polydactylous heterozygotes revealed an A/T transversion mutation that resulted in substitution of a lysine codon with a stop (nonsense) codon at position 145. Alx4m1Yzcm homozygous mice exhibited multiple abnormalities, including extensive preaxial polydactyly of all four limbs (up to seven digits) and the formation of omphalocele.